PROJECT SUMMARY Postpartum depressive disorders (PPD;including major and minor depression) constitute a public health crisis with potentially long-term, adverse consequences for the woman, her child and family. Prevention strategies informed by mechanisms are critical to future reduction in morbidity. There is a dearth of information about the underlying neural mechanisms of PPD and how these impact on maternal caregiving. Our investigative team has begun to uncover putative neural biomarkers of PPD including reduced dorsomedial prefrontal cortex (DMPFC) activity to fearful faces and unsustained ventral striatal response to reward. Furthermore, reduced amygdala activity to infant cry was associated with reduced maternal sensitivity. In response to NIMH strategic plan objective 1) 'To promote discovery in the brain and behavioral sciences to fuel research on the causes of mental disorders', and PA-07-081: 'Women's Mental Health in Pregnancy and the Postpartum Period', we aim to elucidate the putative link between neural activity to emotional stimuli, PPD, and perturbations in maternal sensitivity. In response to NIMH strategic plan objective: 2) 'To chart mental illness trajectories to determine when, where, and how to intervene,'we aim to elucidate developmental pathways to postpartum affective neural functioning to enable early identification (i.e. pre-pregnancy) of vulnerable women, and inform personalized prevention and intervention programs. In this application, we propose to conduct one of the first tests of the neural underpinnings of PPD that are relevant to care of the offspring in young women for whom psychiatric history, psychosocial functioning, and own parenting experience are known, via prospective data collection. To this end, we leverage the expertise of multiple PIs and the extensive resources of the longitudinal Pittsburgh Girls Study (PGS;R01 MH056630) to provide the developmental context to parse the heterogeneity in postpartum affective neural functioning. One hundred and eighty eligible girls aged 18 years and older, who become pregnant during the period of the proposed work, will be recruited from the PGS sample (n=2,451), that has been followed annually for 10 years since ages 5-8 years. We will acquire 3-month postpartum affective neural activity and 3- and 6-month mother-infant interactional data in three sub-groups of women: 1) PPD + past history of major or minor depression;2) PPD + no history of depression;and 3) Healthy postpartum controls with no history of depression. We will thus capitalize on a rare opportunity to elucidate the neural signature of PPD and impairments in maternal sensitivity within a developmental context. PUBLIC HEALTH RELEVANCE: PROJECT NARRATIVE RELEVANCE TO PUBLIC HEALTH Postpartum depressive disorders affect more than one in seven American women annually and can lead to deficits in maternal caregiving that are associated with long-term, adverse consequences for the developing child. By examining brain activity to emotional stimuli in mothers for whom psychosocial background was documented through a 10-year prospective study, we will be able to characterize the neural basis of postpartum depression and maternal caregiving within a developmental context. In so doing, we aim to identify women most at risk for postpartum depression and/or impaired caregiving before pregnancy, and thus facilitate preventive identification and treatment for postpartum depression.